title: [Dexamethasone and vorinostat cooperatively promote differentiation and apoptosis in Kasumi-1 leukemia cells through ubiquitination and degradation of AML1-ETO].
abstract: OBJECTIVE
  To probe the effects of dexamethasone (DEX) combined with histone deacetylase (HDAC) inhibitor vorinostat on inhibiting proliferation and inducing differentiation and apoptosis in Kasumi-1 leukemia cells, and its possible mechanisms in order to provide a theoretical basis for the treatment of AML1-ETO positive AML.
  
  
  METHODS
  The cell survival, differentiation and apoptosis rates were tested by MTT or flow cytometry analysis after Kasumi-1 cells were treated by DMSO, DEX (20 nmol/L), vorinostat (1 μmol/L) or DEX (20 nmol/L) in combination with vorinostat (1 μmol/L). WB and IP-WB were performed to detect AML1-ETO and its ubiquitination.
  
  
  RESULTS
  Treatment with the combination of DEX and vorinostat for 48 h led to statistically significant differences of inhibited proliferation [(42.06±8.20)%], increased differentiation [(52.83±8.97)%] and apoptosis [(52.92±2.53)%] of Kasumi-1 cells when compared with vorinostat [(33.82±9.41)%, (43.93±9.04)% and (42.98±3.01)%, respectively], DEX [(17.30±3.49)%, (22.53±4.51)% and (19.57±2.17)%, respectively] or control [(6.96±0.39)%, (21.73±2.03)% and (6.96±0.39)%, respectively]. Also significant ubiquitination and decreased AML1-ETO protein in Kasumi-1 cells after the combination treatment over single agent or control were observed.
  
  
  CONCLUSIONS
  The results indicated that DEX and vorinostat could synergistically inhibit the Kasumi-1 cells proliferation, induce Kasumi-1 cells differentiation and apoptosis through ubiquitination and degradation of AML1-ETO.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Chen
authors.forename: Jian-wei
authors.initials: JW
authors.lastname: Zhang
authors.forename: Fa-mei
authors.initials: FM
authors.lastname: Xu
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Xing
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tian
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Jian-xiang
authors.initials: JX
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D000075142:RUNX1 Translocation Partner 1 Protein; D054875:Ubiquitination; D000077337:Vorinostat
chemical_list: C107844:AML1-ETO fusion protein, human; D000970:Antineoplastic Agents; D050676:Core Binding Factor Alpha 2 Subunit; D006877:Hydroxamic Acids; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D000077337:Vorinostat; D003907:Dexamethasone